The long range goal of this project is to understand the mechanisms which regulate growth in human pregnancy. Its specific aims for the next granting period are designed to explore the role of two environmental factors (diet and physical activity) and two hormones (HPL and fetal insulin) in prenatal growth regulation. It will test the hypotheses that placental growth rate is altered by diet and physical activity through effects on glucose availability and insulin sensitivity; that HPL and isolated fetal hypo and hyperinsulinemia modulate feto-placental growth; and that placental volume at 20 and 24 weeks is a major determinant of 3rd trimester placental function and size at birth. At 8 weeks gestation, matched subjects will be randomly assigned to one of four exercise and diet regimens which will be continued throughout pregnancy. The impact of these manipulations on glucose and insulin responses and feto-placental growth will be periodically assessed using mixed meal and exercise tolerance testing, stable isotope technology, indirect calorimetry and ultrasound. At delivery neonatal morphometry and biochemical and morphometric indices of placental growth and function will be assessed using standard technology. Additional studies in transgenic mice will evaluate the effect of isolated perturbations in HPL and fetal insulin on similar biochemical and morphometric indices of feto-placental growth and function. The data obtained will extend our knowledge of the role of maternal environmental factors and local hormonal milieu as regulators of feto-placental growth and will allow us to consider the use of specific environmental therapy to modulate feto- placental growth.